論文

査読有り 国際誌
2019年4月11日

STING agonists activate latently infected cells and enhance SIV-specific responses ex vivo in naturally SIV controlled cynomolgus macaques.

Scientific reports
  • Takuya Yamamoto
  • ,
  • Tomohiro Kanuma
  • ,
  • Shokichi Takahama
  • ,
  • Tomotaka Okamura
  • ,
  • Eiko Moriishi
  • ,
  • Ken J Ishii
  • ,
  • Kazutaka Terahara
  • ,
  • Yasuhiro Yasutomi

9
1
開始ページ
5917
終了ページ
5917
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-019-42253-3

To achieve a functional cure for HIV, treatment regimens that eradicate latently HIV-infected cells must be established. For this, many groups have attempted to reactivate latently-infected cells to induce cytopathic effects and/or elicit cytotoxic T lymphocyte (CTL)/NK cell-mediated immune responses to kill these cells. We believe that not only the reactivation of latently-infected cells, but also the induction of strong CTL responses, would be required for this. Here, we used typical immune activators that target pattern recognition receptors (PRRs). For our experimental model, we identified eight SIV-infected cynomolgus monkeys that became natural controllers of viremia. Although plasma viral loads were undetectable, we could measure SIV-DNA by qPCR in peripheral blood mononuclear cells (PBMCs). Using these PBMCs, we screened 10 distinct PRR ligands to measure IFN-α and IFN-γ production. Among these, STING ligands, cGAMP and c-di-AMP, and the TLR7/8 agonist R848 markedly increased cytokine levels. Both R848 and STING ligands could reactivate latently-infected cells in both cynomolgus monkeys and human PBMCs in vitro. Furthermore, c-di-AMP increased the frequency of SIV Gag-specific CD8+ T cells including polyfunctional CD8+ T cells, as compared to that in untreated control or R848-treated cells. Together, STING ligands might be candidates for HIV treatment.

リンク情報
DOI
https://doi.org/10.1038/s41598-019-42253-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30976083
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459902
ID情報
  • DOI : 10.1038/s41598-019-42253-3
  • PubMed ID : 30976083
  • PubMed Central 記事ID : PMC6459902

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